Variant 3-60014216-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 8P and 5B. PVS1BP6BS2

The NM_001320901.2(FHIT):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,551,756 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 9 hom. )

Consequence

FHIT
NM_001320901.2 start_lost

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.708

Variant links:

Genes affected

FHIT (HGNC:3701): (fragile histidine triad diadenosine triphosphatase) The protein encoded by this gene is a P1-P3-bis(5'-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage. [provided by RefSeq, Aug 2017]

FHIT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BP6

Variant 3-60014216-A-G is Benign according to our data. Variant chr3-60014216-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3056428.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIT	NM_002012.4 link	c.104-64T>C		intron_variant		ENST00000492590.6	NP_002003.1	P49789A0A024R366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6 link	c.104-64T>C		intron_variant		1	NM_002012.4	ENSP00000418582.1		P49789

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

623

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.000422

AC:

590

AN:

1399468

Hom.:

AF XY:

0.000382

AC XY:

266

AN XY:

696566

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.000762

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000940

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00410

AC:

624

AN:

152288

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.00475

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FHIT-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 27, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.9

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over